4-(三氟甲基)-(9ci)-1H-苯并咪唑 | 392-11-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 4-(三氟甲基)-(9ci)-1H-苯并咪唑
• 英文名称: 4-(trifluoromethyl)-1H-benzo[d]imidazole
• 英文别名: 4-(trifluoromethyl)-1H-benzo[d]imidazol；4-(trifluoromethyl)benzimidazole；4-trifluoromethyl-1(3)H-benzoimidazole；4-trifluoromethyl-1(3)H-benzimidazole；4-Trifluormethyl-1(3)H-benzimidazol；4-Trifluormethyl-benzimidazol；4-(trifluoromethyl)-1H-benzimidazole
• CAS: 392-11-0
• 化学式: C₈H₅F₃N₂
• mdl: MFCD08741394
• 分子量: 186.136
• InChiKey: FKGDDNPWZXAZFJ-UHFFFAOYSA-N

物化性质

• 熔点：
  192.5 °C
• 沸点：
  339.3±37.0 °C(Predicted)
• 密度：
  1.447±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-(三氟甲基)-(9ci)-1H-苯并咪唑 在 甲醇 、 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 、 sodium methylate 作用下， 反应 3.0h， 生成 1-deoxy-1-(4-(trifluoromethyl)-1H-benzimidazol-1-yl)-β-D-ribofuranose
  参考文献：
  名称：

  RNA RECOGNITION BY FLUOR-AROMATIC SUBSTITUTED

  摘要：

  RNA exhibits a higher structural diversity than DNA and is an important molecule in the biology of life. It shows a number of secondary structures such as duplexes, hairpin loops, bulges, internal loops, etc. However, in natural RNA, bases are limited to the four Predominant structures Q, C, A, and G and so the number of compounds that can be used for investigation of parameters of base stacking, base pairing, and hydrogen bond is limited. We synthesized different fluoromodifications of RNA building blocks: 1'-deoxy- 1'-phenyl-beta-D-ribofuranose (B), 1'-deoxy- 1'-(4-fluorophenyl)-beta-D-ribofuranose (4 FB), 1'-deoxy- 1'-(2,4-difluorophenyl)-beta-D-ribofuranose (2,4 DFB), 1'-deoxy-1'-(2,4,5-trifluorophenyl)-beta-D-ribofuranose (2,4,5 TFB), 1'-deoxy-1'-(2,4,6-trifluorophenyl)-beta-D-ribofuranose, 1'-deoxy- 1'-(pentafluorophenyl)-beta-D-ribofuranose (PFB), 1'-deoxy-1'-(benzimidazol-1-yl)-beta-D-ribofuranose (BI), 1'-deoxy-1'-(4-fluoro- 1H-benzimidazol-1-yl)-beta-D-ribofuranose (4 FBI), 1'-deoxy-1'-(6-fluoro-1H-benzimidazol-1-y1)-beta-D-ribofuranose(6FBI), 1'-deoxy-1'-(4,6-difluoro-IH-benzimidazol-1-yl)-beta-D-ribofuranose(4,6 DFBI), 1'-deoxy-1'-(4-trifluoromethyl-1H-benzimidazol-1-yl)-beta-D-ribofuranose (4 TFM), 1'-deoxy-1'-(5-trifluoromethyl-1H-benzimidazol-1-yl)-beta-D-ribofuranose (5 TFM), and 1'-deoxy-1'-(6-trifluoromethyl- 1H-benzimidazol-1-yl)-beta-D-ribofuranose (6 TFM). These amidites were incorporated and tested in a defined A, U-rich RNA sequence (12-mer, 5'-CUU UUC XUU CUU-3' paired with 3'-GAA AAG YAA GAA-5'). Ono one position was modified, marked as X and Y, respectively. UV melting profiles of those oligonucleotides were measured.

  DOI：

  10.1081/ncn-200059755
• 作为产物：
  描述：

  2-硝基-3-(三氟甲基)苯胺 在 盐酸 、 乙醇 、 tin(ll) chloride 作用下， 生成 4-(三氟甲基)-(9ci)-1H-苯并咪唑
  参考文献：
  名称：

  Sykes; Tatlow, Journal of the Chemical Society, 1952, p. 4078

  摘要：

  DOI：

文献信息

• Selective C–H trifluoromethylation of benzimidazoles through photoredox catalysis
  作者：Guo-Lin Gao、Chao Yang、Wujiong Xia

  DOI：10.1039/c6cc08975e

  日期：——

  This protocol presented a new strategy for visible-light induced C-H trifluoromethyltion at C4 of benzimidazoles using Togini's reagent in the presense of fac-Ir(ppy)3. It's Highlighted by its operational simplicity, mild...

  该协议提出了一种新的策略，以fac-Ir（ppy）3为代表，使用Togini试剂在苯并咪唑的C4处引起CH三氟甲基CH的三氟甲基化反应。它以其操作简单，温和而着称。
• [EN] SUBSTITUTED BENZIMIDAZOLE CARBOXAMIDES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS<br/>[FR] BENZIMIDAZOLE CARBOXAMIDES SUBSTITUÉS ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES MÉDICAUX
  申请人：BIAL BIOTECH INVEST INC

  公开号：WO2021055591A1

  公开（公告）日：2021-03-25

  The invention provides substituted benzimidazole carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

  这项发明提供了替代苯并咪唑羧酰胺及相关化合物，含有这些化合物的组合物，医疗工具包，以及使用这些化合物和组合物治疗患者的医疗疾病的方法，例如癌症、溶酶体贮积症、神经退行性疾病、炎症性疾病。
• Visible-Light-Induced Trifluoromethylation of Highly Functionalized Arenes and Heteroarenes in Continuous Flow
  作者：Jesus Alcazar、Timothy Noёl、Irini Abdiaj、Cecilia Bottecchia

  DOI：10.1055/s-0036-1588527

  日期：2017.11

  We report a continuous-flow protocol for the trifluoromethylation of arenes, heteroarenes, and benzofused heterocycles. This photoredox methodology relies on the use of solid sodium trifluoromethanesulfinate (CF3SO2Na) as the trifluoromethylating agent and the iridium complex [IrdF(CF3)ppy}2](dtbpy)]PF6 as the photoredox catalyst. A diverse set of highly functionalized heterocycles proved compatible with the methodology, and moderate to good yields were obtained within 30 minutes of residence time.

  我们报告了一种用于芳烃、杂环化合物和苯并杂环化合物三氟甲基化的连续流程。这种光氧还原方法依赖于固体三氟甲磺酰亚铁钠（CF3SO2Na）作为三氟甲基化试剂，以及铱配合物[IrdF(CF3)ppy}2](dtbpy)]PF6作为光氧还原催化剂。多样化的高度官能化杂环化合物证明与该方法兼容，并且在30分钟的停留时间内获得了中等至良好的产率。
• Metabolism-Guided Selective Androgen Receptor Antagonists: Design, Synthesis, and Biological Evaluation for Activity against Enzalutamide-Resistant Prostate Cancer
  作者：Dong-Jin Hwang、Yali He、Suriyan Ponnusamy、Thirumagal Thiyagarajan、Michael L. Mohler、Ramesh Narayanan、Duane D. Miller

  DOI：10.1021/acs.jmedchem.2c01858

  日期：2023.3.9

  while retaining potent antagonistic activity for an AR. This structure–activity relationship (SAR) study of more than 50 compounds classified with three classes (Class I, II, and III) and discovered two compounds (32c and 35i) that are potent AR antagonists (e.g., IC50 = 0.021 μM, T1/2 = 120 min for compound 35i). The new antagonists exhibited improved in vivo pharmacokinetics (PK) with high efficacy antiandrogen

  雄激素受体（AR）拮抗剂领域新药发现的一个主要挑战在于预测可成药特性，这些特性将使小分子在体外和体内的进一步研究中保持其效力和稳定性。Indole（化合物8）是一种一流的 AR 拮抗剂，具有非常高的效力 (IC 50 = 0.085 μM)，但代谢不稳定。在本文描述的代谢研究中，我们合成了新的小分子，其稳定性显着提高，同时保留了对 AR 的有效拮抗活性。这项构效关系 (SAR) 研究将 50 多种化合物分为三类（I、II 和 III 类），并发现了两种化合物（32c 和35i）是有效的 AR 拮抗剂（例如，IC 50 = 0.021 μM，对于化合物35i ， T 1/2 = 120 分钟）。新拮抗剂在过表达 AR (LNCaP-AR) 的 Hershberger 和抗雄激素 Enz-Res 肿瘤异种移植模型中表现出改善的体内药代动力学 (PK) 和高效抗雄激素活性。
• Discovery and optimization of 2-(trifluoromethyl)benzimidazole derivatives as novel ferroptosis inducers in vitro and in vivo
  作者：Yuying Fang、Qingyun Tan、Huihao Zhou、Jun Xu、Qiong Gu

  DOI：10.1016/j.ejmech.2022.114905

  日期：2023.1

  Ferroptosis is implicated in diverse human diseases. Ferroptosis inducers hold great potential for cancer therapy. The existing ferroptosis inducers, however, lack structural diversity, and only a few of them are suitable for in vivo applications. Herein, by phenotypic screenings, we discovered a new ferroptosis inducer FA-S, a 2-(trifluoromethyl)benzimidazole derivative, from which a series of its

  铁死亡与多种人类疾病有关。铁死亡诱导剂在癌症治疗方面具有巨大潜力。然而，现有的铁死亡诱导剂缺乏结构多样性，只有少数适​​合体内应用。在此，通过表型筛选，我们发现了一种新的铁死亡诱导剂FA-S，一种 2-(三氟甲基)苯并咪唑衍生物，并设计合成了一系列类似物以提高其活性。这产生了最有效的化合物FA16，具有单位数微摩尔的铁死亡诱导活性和令人满意的代谢稳定性。进一步的研究表明，FA16通过抑制胱氨酸/谷氨酸逆向转运蛋白 (system X c− ). 值得注意的是，类似物FA16具有比经典系统 X c -抑制剂 erastin 更有利的代谢稳定性，后者不适用于体内研究。FA16通过诱导铁死亡显着抑制 HepG2 异种移植模型中的肿瘤生长。这项工作为新的铁死亡诱导剂提供了一个新的支架，同时也为肝细胞癌的治疗提供了一个有前途的线索。我们的工作揭示了一种合适的体内铁死亡诱导工具，以探索铁死亡的潜在机制以及铁死亡与人类疾病发病机制的相关性。